Douxfils Jonathan, Buckinx Fanny, Mullier François, Minet Valentine, Rabenda Véronique, Reginster Jean-Yves, Hainaut Philippe, Bruyère Olivier, Dogné Jean-Michel
Department of Pharmacy, Namur Thrombosis and Hemostasis Center (NTHC), Namur Research Institute for LIfe Sciences (NARILIS), University of Namur, Namur, Belgium (J.D., F.M., V.M., J.M.D.).
Department of Public Health, Epidemiology and Health Economics, University of Liege, Liege, Belgium (F.B., R., J.Y.R., O.B.).
J Am Heart Assoc. 2014 Jun 6;3(3):e000515. doi: 10.1161/JAHA.113.000515.
Signals of an increased risk of myocardial infarction (MI) have been identified with dabigatran etexilate in randomized controlled trials (RCTs).
We conducted searches of the published literature and a clinical trials registry maintained by the drug manufacturer. Criteria for inclusion in our meta-analysis included all RCTs and the availability of outcome data for MI, other cardiovascular events, major bleeding, and all-cause mortality. Among the 501 unique references identified, 14 RCTs fulfilled the inclusion criteria. Stratification analyses by comparators and doses of dabigatran etexilate were conducted. Peto odds ratio (ORPETO) values using the fixed-effect model (FEM) for MI, other cardiovascular events, major bleeding, and all-cause mortality were 1.34 (95% CI 1.08 to 1.65, P=0.007), 0.93 (95%CI 0.83 to 1.06, P=0.270), 0.88 (95% CI 0.79 to 0.99, P=0.029), and 0.89 (95% CI 0.80 to 1.00, P=0.041). When compared with warfarin, ORPETO values using FEM were 1.41 (95% CI 1.11 to 1.80, P=0.005), 0.94 (95%CI 0.83 to 1.06, P=0.293), 0.85 (95% CI 0.76 to 0.96, P=0.007), and 0.90 (95% CI 0.81 to 1.01, P=0.061), respectively. In RCTs using the 150-mg BID dosage, the ORPETO values using FEM were 1.45 (95% CI 1.11 to 1.91, P=0.007), 0.95 (95% CI 0.82 to 1.09, P=0.423), 0.92 (95% CI 0.81 to 1.05, P=0.228), and 0.88 (95% CI 0.78 to 1.00, P=0.045), respectively. The results of the 110-mg BID dosage were mainly driven by the RE-LY trial.
This meta-analysis provides evidence that dabigatran etexilate is associated with a significantly increased risk of MI. This increased risk should be considered taking into account the overall benefit in terms of major bleeding and all-cause mortality.
在随机对照试验（RCT）中已发现达比加群酯有增加心肌梗死（MI）风险的信号。
我们检索了已发表的文献以及由药品制造商维护的临床试验注册库。纳入我们荟萃分析的标准包括所有RCT以及MI、其他心血管事件、大出血和全因死亡率的结局数据。在识别出的501篇独特参考文献中，14项RCT符合纳入标准。对达比加群酯的对照药物和剂量进行了分层分析。使用固定效应模型（FEM）计算的MI、其他心血管事件、大出血和全因死亡率的佩托比值比（ORPETO）值分别为1.34（95%CI 1.08至1.65，P = 0.007）、0.93（95%CI 0.83至1.06，P = 0.270）、0.88（95%CI 0.79至0.99，P = 0.029）和0.89（95%CI 0.80至1.00，P = 0.041）。与华法林相比，使用FEM计算的ORPETO值分别为1.41（95%CI 1.11至1.80，P = 0.005）、0.94（95%CI 0.83至1.06，P = 0.293）、0.85（95%CI 0.76至0.96，P = 0.007）和0.90（95%CI 0.81至1.01，P = 0.061）。在使用每日两次150毫克剂量的RCT中，使用FEM计算的ORPETO值分别为1.45（95%CI 1.11至1.91，P = 0.007）、0.95（95%CI 0.82至1.09，P = 0.423）、0.92（95%CI 0.81至1.05，P = 0.228）和0.88（95%CI 0.78至1.00，P = 0.045）。每日两次110毫克剂量的结果主要由RE-LY试验驱动。
这项荟萃分析提供了证据，表明达比加群酯与MI风险显著增加相关。在考虑大出血和全因死亡率方面的总体益处时，应考虑到这种增加的风险。
